Linking the organization of DNA replication with genome maintenance

被引：0
作者：
Balveer Singh
Pei-Yun Jenny Wu
机构：
[1] CNRS,
[2] University of Rennes,undefined
[3] Institute of Genetics and Development of Rennes,undefined
来源：
Current Genetics | 2019年 / 65卷
关键词：
DNA replication; Replication program; S phase checkpoint; Genome instability; Replication stress; DNA damage; Rad3/ATR (ataxia telangiectasia and Rad3-related); Fission yeast;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The spatial and temporal organization of genome duplication, also referred to as the replication program, is defined by the distribution and the activities of the sites of replication initiation across the genome. Alterations to the replication profile are associated with cell fate changes during development and in pathologies, but the importance of undergoing S phase with distinct and specific programs remains largely unexplored. We have recently addressed this question, focusing on the interplay between the replication program and genome maintenance. In particular, we demonstrated that when cells encounter challenges to DNA synthesis, the organization of DNA replication drives the response to replication stress that is mediated by the ATR/Rad3 checkpoint pathway, thus shaping the pattern of genome instability along the chromosomes. In this review, we present the major findings of our study and discuss how they may bring new perspectives to our understanding of the biological importance of the replication program.
引用
收藏
页码：677 / 683
页数：6
相关论文
共 180 条
[1]  
Ahuja AK(2016)A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells Nat Commun 7 10660-6651
[2]  
Jodkowska K(1996)The Schizosaccharomyces pombe rad3 checkpoint gene EMBO J 15 6641-446
[3]  
Teloni F(2011)Nucleotide deficiency promotes genomic instability in early stages of cancer development Cell 145 435-1052
[4]  
Bentley NJ(2005)Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint Genes Dev 19 1040-204
[5]  
Holtzman DA(2010)The DNA damage response: making it safe to play with knives Mol Cell 40 179-3690
[6]  
Flaggs G(2012)Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells EMBO J 31 3678-2299
[7]  
Bester AC(2009)Predictable dynamic program of timing of DNA replication in human cells Genome Res 19 2288-363
[8]  
Roniger M(2009)Fragile genomic sites are associated with origins of replication Genome Biol Evol 1 350-89
[9]  
Oren YS(2013)DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability Semin Cancer Biol 23 80-398
[10]  
Byun TS(1999)A Rad3-Rad26 complex responds to DNA damage independently of other checkpoint proteins Nat Cell Biol 1 393-1107
12345678910